Hidetoshi Tsukamoto

Hiroshima Prefectural University, Hirosima, Hiroshima, Japan

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Publications (53)70.84 Total impact


  • No preview · Article · Jan 2014
  • H. Sakurashita · T. Tomita · H. Ikeda · H. Tsukamoto · K. Kihira
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    ABSTRACT: Purpose: To compare the daily cost of latanoprost ophthalmic solution between brand and generic products. Method: This study was made on Xalatan ® and other 22 generic brands of latanoprost ophthalmic solution. Each product was tested for total number of drops to count how many days can be used for one bottle. Actual cost per day was also estimated. Results: Volume of one drop was 31.9 μ1 for Xalatan® and 28.4 to 38.μ1 for generic brands. Content of one bottle lasted, theoretically, 45 days for Xalatan® and 34 to 49 days for generic brands. Daily cost for Xalatan® was 50.8 yen and 31.2 to 45.5 yen for the rest. Conclusion: Actual daily cost of latanoprost ophthalmic solution of generic products ranged from 61 to 89% to that of Xalatan®.
    No preview · Article · Jul 2011
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    ABSTRACT: Timolol, a beta-blocker, has been shown to be an effective ocular hypotensive agent when used alone or with carbonic anhydrase inhibitor on ocular hypertensive or open angle glaucoma patients. The effect of timolol hemihydrate on the CO(2) hydration activities of human carbonic anhydrase (HCA) I and II and their reaction mechanisms were investigated. Timolol activates the enzyme activities of HCA I and HCA II. In HCA I and II, the enzyme kinetic results clearly showed that timolol increases the value of V(max) but does not influence the value of K(m). The enzyme kinetic method showed that timolol noncompetitively activates HCA I and II activities through the formation of a ternary complex consisting of the enzyme, the substrate, and timolol. These results indicate that timolol binds apart from the narrow cavity of the active site. AutoDocking results showed that timolol binds at the entrance of the active site cavity in a region where the proton shuttle residue, His 64, of HCA I or II, is placed. The enzyme kinetic and AutoDocking results showed that timolol might weakly bind near the proton shuttle residue, His 64, to accelerate the proton transfer rate from His 64 to the buffer components. It is known that efficient activators of carbonic anhydrase possess a bulky aromatic/heterocyclic moiety and a primary/secondary amino group in their molecular structure. Timolol has a heterocyclic moiety and a secondary amino group, which are typical structures in efficient activators of carbonic anhydrase.
    No preview · Article · Feb 2010 · Biological & Pharmaceutical Bulletin
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    ABSTRACT: Latanoprost, a prostaglandin F2 alpha analogue, has been shown to be an effective ocular hypotensive agent when used alone on ocular hypertensive or open angle glaucoma patients. Carbonic anhydrase (CA) inhibitors are also used to reduce ocular hypertension by decreasing aqueous humor secretion, and are given in combination with prostaglandin F2 alpha analogue. It has been shown that prostaglandin F2 alpha, Minprostin F2 alpha, has been shown to increase the carbonic anhydrase (CA) activity and blood pressure. However, the effects of latanoprost on CA have not been clarified. Therefore, we studied the effects of latanoprost free acid on human carbonic anhydrase (HCA) I and II using the stopped flow method. Latanoprost free acid inhibited the hydration activity of HCA I or II by a noncompetitive mechanism. The inhibition constants (Ki) of latanoprost free acid for HCA I and II were 0.22 and 2.3 mM, respectively. Therefore, latanoprost free acid is a weak inhibitor of HCA I or II. AutoDock simulation of the latanoprost free acid-HCA I or II complex showed that the carboxylic moiety of latanoprost free acid, which is located at the end of the molecule, binds to the zinc ion of the active site by stretching of the chain of latanoprost free acid through the narrow and deep active site cavity of HCA I or II. In the active site cavity of HCA I or II, one side is hydrophilic and the other is hydrophobic. AutoDock simulation results clearly showed that latanoprost free acids lie down on the hydrophobic sides of the active site cavities in HCA I and II. The noncompetitive inhibition mechanism and the binding mode of latanoprost free acid indicate that the behavior of latanoprost free acid is very similar to that of simple anions.
    No preview · Article · Jun 2008 · Biological & Pharmaceutical Bulletin
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    ABSTRACT: Purpose: To non-invasively measure corneal displacement as an index of corneal stiffness and estimate its correlation with age and ocular parameters. Methods: We examined 104 normal human eyes (54 male and 50 female). Corneal deformation caused by an air jet from a non-contact tonometer was monitored using a high-speed camera, and the corneal displacement was calculated. The correlation of corneal displacement with age and ocular parameters, such as intraocular pressure (IOP), central corneal thickness, corneal curvature, corneal endothelial cell density, axial length, and spherical equivalent, was estimated by multivariate analysis. To investigate the effect of aging on corneal displacement, the subjects were divided into young and elderly groups; significant inter-group differences were estimated by the Mann-Whitney test. Results: Corneal displacement significantly correlated with age and IOP but not with other parameters. Corneal displacement was significantly greater in the elderly group than in the young group, although no significant difference in IOP was observed. Conclusions: Aging may affect corneal displacement.
    No preview · Article · Jun 2008 · Folia Japonica de Ophthalmologica Clinica
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    ABSTRACT: Goldmann applanation tonometry is commonly used for measuring intraocular pressure (IOP) to diagnose glaucoma. However, the measured IOP by conventional applanation tonometry is valid only under the assumption that all subjects have the same structural eye stiffness. This paper challenges in vivo measurement of eye stiffness with a noninvasive approach and investigates individual differences of eye stiffness. Eye stiffness is defined by the applied force and displacement of the cornea. The displacement is detected based on captured images by a high resolution camera. The experimental results show that the measured stiffness nicely matches the analytical result that is derived from a simple spherical deformation model with an internal pressure. However, some subjects have different eye stiffness even with the same IOP. IOP with abnormal stiffness may be over/underestimated by conventional applanation tonometry. The proposed eye stiffness measurement can help detect the misestimated eye and it contributes to the early detection of glaucoma.
    Full-text · Article · Mar 2008 · IEEE transactions on bio-medical engineering
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    ABSTRACT: The clinical significance of a proper eye drop application technique was evaluated in Japanese glaucoma patients. Patients diagnosed with primary open-angle glaucoma having intraocular pressure (IOP) greater than 21 mmHg were treated with eye drops at home. In some patients, however, the topical treatment was ineffective. They returned to the hospital to receive surgical treatment. On admission, 56% of these patients had IOP greater than 21 mmHg. Patient instillation technique was evaluated based on the proximity of the eyedropper tip to the eyes, application position, eyelid closure, treatment (removal) of excess fluid, and nasolacrimal occlusion. In addition, pharmacists interviewed patients to determine the level of understanding of glaucoma, knowledge of prescribed drugs, home application technique, and sensation after application. Multivariate analysis revealed that the key factors influencing the control of IOP to less than 21 mmHg with topical medication were: application of drops in the center of the eye and removal of excessive fluid, in addition to gender and age. Proper topical application at home was dependent on the patient's understanding of the disease, knowledge of prescribed drugs, patient education on the use of drugs, the competence of the instructor, and knowledge of correct application technique. This study indicates that easily comprehensible patient education on the use of eye drops, the nature of glaucoma and the proper use of prescribed drugs is vital to improving the clinical efficacy of topical ophthalmic medication of glaucoma in adult patients.
    Full-text · Article · Feb 2008 · Pharmazie
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    ABSTRACT: To investigate whether the aqueous levels of vascular endothelial growth factor (VEGF) and interleukin-6 (IL-6) are correlated to the vitreous levels of these substances and to the severity of macular oedema in branch retinal vein occlusion (BRVO). Aqueous and vitreous samples were obtained during cataract and vitreous surgery from 24 patients (24 eyes) with macular oedema in BRVO. The VEGF and IL-6 levels in aqueous humour, vitreous fluid, and plasma were determined by enzyme-linked immunosorbent assay. The degree of retinal ischaemia was evaluated in terms of the area of capillary nonperfusion using the Scion Image. The severity of macular oedema was evaluated using the OCT. The aqueous level of VEGF was significantly correlated with the vitreous level of VEGF (P<0.0001). Vitreous levels of VEGF and IL-6 were significantly correlated with the nonperfusion area of BRVO (P<0.0001, P=0.0061, respectively), as were the aqueous levels of VEGF and IL-6 (P<0.0001, P=0.0267, respectively). Furthermore, the vitreous levels of VEGF and IL-6 and the aqueous level of VEGF were significantly correlated with the severity of macular oedema of BRVO (P=0.0001, P=0.0331, P=0.0272, respectively). Our results suggest that the aqueous level of VEGF may reflect its vitreous level. Measurement of the aqueous level of VEGF may be clinically useful to indicate the severity of macular oedema with BRVO.
    Preview · Article · Feb 2008 · Eye
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    ABSTRACT: The contact tonometer is commonly used for measuring the internal eye pressure to diagnose glaucoma. However, the conventional eye pressure measurement is valid only under the assumption that all subjects have the same structural eye stiffness. This paper challenges to measure the contact area between the probe and the cornea in addition to the corneal deformation for considering the individual differences in the structural eye stiffness. Prior to the experiment, a spherical model of an eye is developed and the analytical eye stiffness is introduced. The experiment is conducted based on the contact method where a contact probe is pressed on an anesthetized cornea. The deformation of the cornea and the contact area are captured by cameras during the experiment. The experimental results show that the measured stiffness nicely matches the analytical solution based on the constructed model. However, some subjects have different relationships between the displacement and the contact area even with similar estimated eye pressures. This suggests that the structural eye stiffness should be considered for more precise diagnoses of glaucoma.
    No preview · Conference Paper · May 2007
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    ABSTRACT: To compare the mean transit time (MTT) of retinal circulation in eyes with primary open-angle glaucoma (POAG) and eyes with normal-tension glaucoma (NTG) and examine the possible relationship between MTT and visual field damage, expressed as mean deviation (MD). Video fluorescein angiography was performed in 40 patients with POAG or NTG. Dye curves for fluorescein passing through the retinal arteries and veins were used to calculate MTT in each patient with a computer-assisted technique based on an impulse-response analysis (MTT(IR)). We were able to analyse MTT(IR) in all 40 angiograms. Mean (SD) MTT(IR) was 5.0 (1.5) seconds in eyes with POAG and 4.7 (1.4) seconds in eyes with NTG. The difference was not statistically significant. There was a weak but significant correlation between the MD and MTT(IR) (MTT(IR) = 4.12-0.08*MD; r = -0.49, p = 0.0013). The results demonstrate that loss of neuronal tissue in glaucoma is combined with an effect on the retinal circulation and that the effect is similar in eyes with NTG and eyes with POAG.
    Preview · Article · Mar 2007 · Acta Ophthalmologica Scandinavica
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    ABSTRACT: Through the observation of the eye deformation during an air jet application, we found that the eye deformation is always delayed with respect to the starting time of the air jet application. In order to explain such a characteristic, we newly introduce the cornea chain model, which assumes that the surface can be bent without any resistance under zero internal pressure, while it can not be deformed under an adequate internal pressure. We show that the chain model can nicely explain the characteristic distribution in the cornea deformation. Furthermore, we show that a pretty high correlation (R=0.816) exists between the delay time and the estimated internal eye pressure. This result can be used in a new type of a non-contact tonometer, which measures the internal eye pressure based on the delay time and which is gentler for eyes than the conventional one.
    Preview · Article · Jan 2007
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    ABSTRACT: The internal eye pressure is an important index for judging whether an eye suffers from glaucoma or not. The conventional eye pressure measurement is valid only under the condition that all subjects have the same structural eye stiffness. This paper challenges stiffness sensing of a living human eye by pressing with a contact probe. Prior to the experiment, a spherical model of an eye is developed and the analytical eye stiffness is introduced. The experiment is conducted based on the contact method where a contact probe is pressed on an anesthetized cornea. The deformation of the cornea is captured by a camera with high resolution during the experiment. The experimental results show that the measured stiffness nicely matches the analytical solution based on the constructed model.
    Preview · Article · Jan 2007
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    ABSTRACT: We investigated the differential protein expression patterns of retinal pigment epithelial (RPE) cells exposed to increased glucose concentrations. Cultured human RPE cells (ARPE-19) were exposed for 4 days with normal blood glucose concentration (5.5 mM D-glucose), followed by exposure to either normal (5.5 mM) or high (33 mM) concentrations of D-glucose for 48h. Protein extracts of glucose-treated RPE cells were then subjected to comparative proteome analysis based on 2-D gel electrophoresis. Protein spots were visualized by silver staining. The differentially expressed proteins were excised and digested in-gel with trypsin, then analysed by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). The expression levels of cathepsin B, glutathione peroxidase and heat shock protein 27 were increased, and that of protein disulfide isomerase decreased in high glucose treated RPE compared to normal glucose. The isoelectric point of copper/zinc-containing superoxide dismutase (Cu/Zn-SOD) shifted toward acidic region in response to high glucose. Cu/Zn-SOD activity in high glucose group was significantly lower than that in normal glucose group (P<0.05, Mann-Whitney U-test). Systematic survey of protein expression has revealed that RPE cells respond to acute, pathologically high glucose levels by the elevated expression of anti-oxidant and proteolytic enzymes.
    No preview · Article · Oct 2006 · Experimental Eye Research
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    ABSTRACT: For the diagnosis and treatment of glaucoma, a reliable and non-invasive measurement method of the internal eye pressure, i.e. the intraocular pressure (IOP), is desired. The IOP resists a deformation of the eye and thus non-contact tonometers, which deform the eye by a short air pulse, are suitable to estimate the IOP. By monitoring the reflection of an incident infrared light, the tonometer measures the time an applied air jet flattens part of the eye. The relationship between flattening time and IOP are provided by calibration. In our work, we used an additional high speed camera to capture the eye deformation directly and obtain more data during the pressure measurement. We show that the principle shape of the deformation can be understood by assuming simple non-linear material properties of the cornea in an eye model. Furthermore, we discuss which sources of error are still needed to be overcome to give a medical meaningful diagnosis for the examined eye by the data from the high speed camera
    No preview · Conference Paper · Oct 2006
  • Hidetoshi Tsukamoto · Satoshi Mukai · Aiko Iwase · Hiromu K Mishima
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    ABSTRACT: In frequency doubling technology (FDT) perimetry, the incidence of tests classified as unreliable is higher in the second-tested left eye than in the first-tested right eye when perimetry is performed without a rest period. The purpose of this study was to determine whether the incidence of unreliable results was reduced when the retest began after a 5-min rest period. The subjects were 978 residents of Miyoshi City, Japan, who underwent FDT perimetry during a medical checkup. FDT perimetry was always performed first on the right eye and then on the left eye without a rest interval. When the results were determined to be unreliable, FDT perimetry was repeated after a 5-min rest interval. The perimetric results were determined to be unreliable in one eye of 119 subjects; the results of the first-tested right eye were unreliable in 24 (20.2%), and the results of the second-tested left eye were unreliable in 95 (79.8%) subjects. This difference in the incidence of reliability was significant (P<0.001). After a 5-min rest interval, the percentage of eyes with reliable results recovered to 92% of the right eyes and to 86% of the left eyes. The incidence of unreliable results in FDT perimetry of the second-tested left eye was higher than that of the first-tested right eye when tests were performed without a rest interval. However, the incidence of unreliability in the eye was decreased when the retest was performed after a 5-min rest interval.
    No preview · Article · Aug 2006 · Japanese Journal of Ophthalmology
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    Y. Kurita · Y. Iida · R. Kempf · M. Kaneko · E. Sugimoto · H. Tsukamoto · H.K. Mishima
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    ABSTRACT: The internal eye pressure is an important index for judging whether an eye suffers from glaucoma or not. The conventional eye pressure measurement is valid only under the condition that all subjects have the same structural eye stiffness. This paper challenges stiffness sensing of the human eye by pressing it with a contact probe. The displacement of the eye is captured by a camera with high resolution. Experimental results show that the stiffness is roughly constant for each subject, while it differs by up to a factor of five between subjects. The method can detect subjects whose eye stiffness is smaller than average for further careful medical examination
    Full-text · Conference Paper · Jun 2006
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    ABSTRACT: To compare the prevalence of glaucoma in adults with Down's syndrome (DS) to that in non-DS control adults. Twenty-six patients (14 men and 12 women) with DS and 188 control subjects (105 men and 83 women) were studied. The mean age was 35.1 +/- 6.9 (+/- SD) years in the DS group and 36.9 +/- 5.2 years in the control group. There were no significant differences in age or sex distribution between the two groups. Glaucoma was diagnosed by two glaucoma specialists based on the optic disc findings obtained through dilated pupils. The prevalence of patients with glaucoma in the DS group was 11.5%, significantly higher (P = 0.014) than that in the control group, 1.1%. There was no significant difference in intraocular pressure between glaucomatous eyes (12.2 +/- 3.2 mmHg) and nonglaucomatous eyes (11.1 +/- 4.1 mmHg) in the DS group (P = 0.465). The prevalence of glaucoma in adult patients with DS was significantly higher than that in age-matched control subjects.
    No preview · Article · Jun 2006 · Japanese Journal of Ophthalmology
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    ABSTRACT: To investigate whether vascular endothelial growth factor (VEGF) or interleukin-6 (IL-6) contributes to the pathogenesis of macular edema in eyes with branch retinal vein occlusion (BRVO), the correlations between these factors were investigated. We studied 25 patients suffering from macular edema with BRVO and 14 patients with nonischemic ocular disease (control group). The degree of retinal ischemia was evaluated in terms of the area of capillary nonperfusion using Scion Images, and the severity of macular edema was examined using optical coherence tomography. Vitreous fluid samples were obtained at the time of vitreoretinal surgery, and VEGF and IL-6 levels in the vitreous fluid and plasma were determined by means of enzyme-linked immunosorbent assays. Vitreous fluid levels of VEGF and IL-6 were significantly elevated in patients with BRVO compared with control patients (P = 0.0011 and P < 0.0001, respectively). Also, the vitreous level of VEGF was significantly correlated with that of IL-6 (P = 0.0012), and vitreous levels of VEGF and IL-6 were correlated with the size of the BRVO nonperfusion area (P < 0.0001 and P = 0.0033, respectively). Furthermore, vitreous levels of VEGF and IL-6 were correlated with the severity of macular edema (P = 0.0008 and P = 0.0191, respectively) and the severity of macular edema of BRVO was significantly correlated with the size of the BRVO nonperfusion area (P=0.0044). The levels of VEGF and IL-6 are increased in patients with macular edema with BRVO and are significantly correlated with the size of the nonperfusion area and the severity of macular edema. Therefore, they may play a role in macular edema with BRVO.
    No preview · Article · Mar 2006 · Albrecht von Graæes Archiv für Ophthalmologie
  • Hidetoshi Tsukamoto · Hidetaka Noma · Hiromu K Mishima
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    ABSTRACT: Without Abstract
    No preview · Article · Feb 2006 · Japanese Journal of Ophthalmology
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    ABSTRACT: The internal eye pressure is an important index for judging whether an eye suffers from glaucoma or not. The conventional eye pressure measurement is valid only under the condition that all subjects have the same structural eye stiffness. This paper challenges the practice of measuring the stiffness of a human eye by pressing the cornea with a contact probe. The displacement of the eye is captured by a camera with high resolution. Experimental results suggest that the measured eye stiffness nicely matches with the theoretical estimation. Based on the experimental results, the difference between the eye stiffness measured by the contact method and the non-contact method is discussed.
    Preview · Article · Feb 2006 · Conference proceedings: ... Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Conference

Publication Stats

773 Citations
70.84 Total Impact Points

Institutions

  • 2004-2008
    • Hiroshima Prefectural University
      Hirosima, Hiroshima, Japan
  • 2000-2006
    • Hiroshima University
      • • Graduate School of Engineering
      • • Department of Ophthalmology and Visual Science
      • • Department of Ophthalmology
      Hirosima, Hiroshima, Japan